Rat myoblastic sarcoma cell lines. A model for the study of invasion, metastasis, and myogenic differentiation

Abstract

Background: To understand the relation between differentiation and metastasis and to identify genes involved in invasive or metastatic potential of cancer cells it is necessary to develop experimental models allowing in vivo and in vitro studies.

Experimental design: Cell lines with definite metastatic potentials have been established and cloned from a metastatic nodule of an induced rhabdomyosarcoma in syngeneic F344 rats. The parental cell line, SMF-A, is tumorigenic, highly invasive and metastatic. Another cell line, SMF-D, derived from the parental cell line, is also tumorigenic but not metastatic. Biopathologic differences between the metastatic and nonmetastatic SMF cell lines have been studied.

Results: The loss of metastatic potential of the SMF-D cell line was found to be stable and was accompanied by changes in in vitro invasiveness and in myogenic differentiation state. An immunohistochemical study of the expression of cytoskeletal proteins (vimentin, desmin, alpha-actins) indicates that desmin is undetectable in metastatic SMF-A cells, whereas it is strongly expressed in the nonmetastatic SMF-D cells. However, the two cell lines express vimentin but not sarcomeric alpha-actin. These observations suggest that SMF-A cells are of undifferentiated premyoblastic type and SMF-D cells, of myoblastic type. Our study suggests an association between the appearance of myogenic differentiation and the loss of metastatic potential in the SMF-D cell line.

Conclusions: This rat myoblastic sarcoma model may prove useful for in vivo and in vitro studies of the metastatic potential of tumor cells. This model also lends itself to studies of the relation between invasive or metastatic potential and differentiation since the steps of myogenic differentiation are well known.